Science Bite (3 minute oral presentation with PPT in live session with pre-recorded e-poster) Lorne Infection and Immunity 2021

Identifying novel Vgamma9Vddelta2 T cell phenotypes during human Plasmodium falciparum infection (#110)

Nicholas L Dooley 1 , Jessica R Loughland 1 , Dean W Andrew 1 , James S McCarthy 1 , Michelle J Boyle 1
  1. QIMR Berghofer / Griffith University, Herston, QLD, Australia

Increasing evidence shows that repeat exposures to Plasmodium falciparum (Pf) alone does not induce the development of long-lived malaria immunity, and current vaccinations that target antibody responses have short-lived protection. Vg9Vd2 T cells are an innate-like subset of T cells which are essential to the inflammatory immune response to malaria. Alongside inflammatory responses, we propose Vg9Vd2 cells may also act as antigen-presenting cells (APCs) or take on T follicular helper (TfH) cell like characteristics during Pf infection to contribute to parasite-specific antibody development. Recently, we observed the emergence of these adaptive Vg9Vd2 T cell phenotypes during a Controlled Human Malaria Infection (CHMI). In this CHMI, malaria-naive Australian adults were intravenously inoculated with 2,800 intact 3D7-Pf parasitised red blood cells (pRBCs), and blood drawn at days 0, 4, 8, 15 and 45 post-infection (n = 8).  Whole blood staining showed increased Vg9Vd2 T cell surface expression of APC-marker HLA-DR, and Tfh-related markers CD40L and CXCR5 at 15 days post infection. To confirm these findings in vitro, PBMCs from malaria-naive adults were stimulated with pRBCs for 72 hours. We observed increase surface antibody frequencies of CD86, HLA-DR, CD40L and CXCR5 compared to uninfected RBC and blank media cultures. Surface phenotypes were characterised by fluorescent antibody detection using a BD LSR Fortessa 5 flow cytometer. Data generated identifies an unconventional adaptive Vg9Vd2 T cell phenotype activated during Pf infection. Modulation of the gd T cell adaptive immune response in malaria could have significant implications on pathogenesis and symptomatic disease